tbuckley/cabot-search huggingface dataset:
Discriminating Inflammatory Radiation-Related Changes From Early Recurrence in Patients With Glioblastomas
Authors: Aurélie Moreau, Fouzi Khayi, Aurélien Maureille, Alice Bonneville-Levard, Louis Larrouquere, François Ducray, David Kryza
Journal: Clinical Nuclear Medicine (2023)

Purpose of the Report Using morphological and functional imaging to discriminate recurrence from postradiation-related modifications in patients with glioblastomas remains challenging. This pilot study aimed to assess the feasibility of using 68 Ga–prostate-specific membrane antigen (PSMA) 11 PET/CT compared with 18 F-FDOPA PET/CT to detect early recurrence. Methods Nine patients followed up for glioblastomas who received MRI during 12 months of follow-up were referred for both 68 Ga-PSMA-11 and 18 F-FDOPA PET/CT. The SUV max , lesion-to-striatum ratio, lesion-to-normal parenchyma ratio, and lesion-to-salivary gland ratio were calculated. Results Good correlation between 18 F-FDOPA and 68 Ga-PSMA PET/CT findings was seen in 5 patients. In 4 patients, the findings of both examinations were consistent with recurrence but were better visualized with the PSMA PET/CT. Examinations of the fifth patient were suggestive of postradiation-related changes and were better analyzed with the PSMA PET/CT, which displayed relatively low uptake compared with DOPA PET/CT. Conversely, 4 patients showed conflicting results: recurrence was not detected on the PSMA PET/CT because of previously introduced bevacizumab treatment; in another patient, both examinations were consistent with recurrence, but there was an uptake mismatch at the suspected lesion sites, and 2 patients presented with inconsistent findings. Conclusions Despite a few discrepancies, this study highlights the potential role of 68 Ga-PSMA-11 PET/CT for discriminating postradiation inflammation from recurrence. 68 Ga-PSMA-11 PET/CT has an excellent lesion-to-background ratio, and false-positive and false-negative results could be minimized through implementing certain protocols before performing the examination. More powerful prospective studies are required to validate our results.
An immediate way to lower pandemic risk: (not) seizing the low-hanging fruit (bat)
Authors: Steven A Osofsky, Susan Lieberman, Christian Walzer, Helen L Lee, Laurel A Neme
Journal: The Lancet Planetary Health (2023)

What is the least that humanity can do to mitigate the risks of future pandemics, to prevent worldwide surges in human deaths, illness, and suffering—and more waves of multitrillion US dollar impacts on the global economy? The issues around our consumption and trading of wildlife are diverse and complex, with many rural communities being dependent on wild meat for their nutritional needs. But bats might be one taxonomic group that can be successfully eliminated from the human diet and other uses, with minimal costs or inconvenience to the vast majority of the 8 billion people on Earth. The order Chiroptera merits genuine respect given all that these species contribute to human food supplies through pollination services provided by the frugivores and to disease risk mitigation delivered by insectivorous species. The global community missed its chance to stop SARS-CoV and SARS-CoV-2 from emerging—how many more times will humanity allow this cycle to repeat? How long will governments ignore the science that is in front of them? It's past time for humans to do the least that can be done. A global taboo is needed whereby humanity agrees to leave bats alone, not fear them or try to chase them away or cull them, but to let them have the habitats they need and live undisturbed by humans. What is the least that humanity can do to mitigate the risks of future pandemics, to prevent worldwide surges in human deaths, illness, and suffering—and more waves of multitrillion US dollar impacts on the global economy? The issues around our consumption and trading of wildlife are diverse and complex, with many rural communities being dependent on wild meat for their nutritional needs. But bats might be one taxonomic group that can be successfully eliminated from the human diet and other uses, with minimal costs or inconvenience to the vast majority of the 8 billion people on Earth. The order Chiroptera merits genuine respect given all that these species contribute to human food supplies through pollination services provided by the frugivores and to disease risk mitigation delivered by insectivorous species. The global community missed its chance to stop SARS-CoV and SARS-CoV-2 from emerging—how many more times will humanity allow this cycle to repeat? How long will governments ignore the science that is in front of them? It's past time for humans to do the least that can be done. A global taboo is needed whereby humanity agrees to leave bats alone, not fear them or try to chase them away or cull them, but to let them have the habitats they need and live undisturbed by humans.
Indigenous communities and the mental health impacts of land dispossession related to industrial resource development: a systematic review
Authors: Melody E Morton Ninomiya, Nicole Burns, Nathaniel J Pollock, Nadia T G Green, Jessica Martin, Janice Linton, Jenny R Rand, Laura Jane Brubacher, Arn Keeling, Alex Latta
Journal: The Lancet Planetary Health (2023)

Globally, many resource extraction projects such as mines and hydroelectric dams are developed on the territories of Indigenous Peoples. Recognising land as a determinant of Indigenous Peoples' health, our objective is to synthesise evidence about the mental health impacts on Indigenous communities who experience land dispossession due to industrial resource development (mining, hydroelectric, petroleum, and agricultural). We systematically reviewed studies that focused on Indigenous land dispossession in Australia, Aotearoa (New Zealand), North and South America, and the Circumpolar North. We searched Scopus, Medline, Embase, PsycINFO, and Global Health on OVID for peer-reviewed articles published in English from database inception to Dec 31, 2020. We also searched for books, research reports, and scholarly journals specialising in Indigenous health or Indigenous research. We included documents that reported on primary research, focused on Indigenous Peoples in settler colonial states, and reported on mental health and industrial resource development. Of the 29 included studies, 13 were related to hydroelectric dams, 11 to petroleum developments, nine to mining, and two to agriculture. Land dispossession due to industrial resource development had predominantly negative mental health impacts on Indigenous communities. The impacts were consequences of colonial relations that threatened Indigenous identities, resources, languages, traditions, spirituality, and ways of life. Health impact assessment processes in industrial resource development must expressly consider risks and potential impacts on mental health and respect Indigenous rights by making knowledge about mental health risks a central component to decisions about free, prior, and informed consent.
Roles of malate and aspartate in gluconeogenesis in various physiological and pathological states
Authors: Milan Holeček
Journal: Metabolism (2023)

Gluconeogenesis, a pathway for glucose synthesis from non-carbohydrate substances, begins with the synthesis of oxaloacetate (OA) from pyruvate and intermediates of citric acid cycle in hepatocyte mitochondria. The traditional view is that OA does not cross the mitochondrial membrane and must be shuttled to the cytosol, where most enzymes involved in gluconeogenesis are compartmentalized, in the form of malate. Thus, the possibility of transporting OA in the form of aspartate has been ignored. In the article is shown that malate supply to the cytosol increases only when fatty acid oxidation in the liver is activated, such as during starvation or untreated diabetes. Alternatively, aspartate synthesized from OA by mitochondrial aspartate aminotransferase (AST) is transported to the cytosol in exchange for glutamate via the aspartate-glutamate carrier 2 (AGC2). If the main substrate for gluconeogenesis is an amino acid, aspartate is converted to OA via urea cycle, therefore, ammonia detoxification and gluconeogenesis are simultaneously activated. If the main substrate is lactate, OA is synthesized by cytosolic AST, glutamate is transported to the mitochondria through AGC2, and nitrogen is not lost. It is concluded that, compared to malate, aspartate is a more suitable form of OA transport from the mitochondria for gluconeogenesis.
Discontinuation of Universal Admission Testing for SARS-CoV-2 and Hospital-Onset COVID-19 Infections in England and Scotland
Authors: Theodore R. Pak, Chanu Rhee, Rui Wang, Michael Klompas
Journal: JAMA Internal Medicine (2023)

This quality improvement study examines the association between the discontinuation of universal admission testing for SARS-CoV-2 infections and hospital-onset SARS-CoV-2 infections in England and Scotland.
Characterization of Transplant Center Decisions to Allocate Kidneys to Candidates With Lower Waiting List Priority
Authors: Kristen L. King, S. Ali Husain, Miko Yu, Joel T. Adler, Jesse Schold, Sumit Mohan
Journal: JAMA Network Open (2023)

Allocation of deceased donor kidneys is meant to follow a ranked match-run list of eligible candidates, but transplant centers with a 1-to-1 relationship with their local organ procurement organization have full discretion to decline offers for higher-priority candidates and accept them for lower-ranked candidates at their center.
Breast Cancer Mutations <i>HER2V777L</i> and <i>PIK3CAH1047R</i> Activate the p21–CDK4/6–Cyclin D1 Axis to Drive Tumorigenesis and Drug Resistance
Authors: Xiaoqing Cheng, Yirui Sun, Maureen Highkin, Nagalaxmi Vemalapally, Xiaohua Jin, Brandon Zhou, Julie L. Prior, Ashley R. Tipton, Shunqiang Li, Anton Iliuk, Samuel Achilefu, Ian S. Hagemann, John R. Edwards, Ron Bose
Journal: Cancer Research (2023)

Abstract In metastatic breast cancer, HER2-activating mutations frequently co-occur with mutations in PIK3CA, TP53, or CDH1. Of these co-occurring mutations, HER2 and PIK3CA are the most commonly comutated gene pair, with approximately 40% of HER2-mutated breast cancers also having activating mutations in PIK3CA. To study the effects of co-occurring HER2 and PIK3CA mutations, we generated genetically engineered mice with the HER2V777L; PIK3CAH1047R transgenes (HP mice) and studied the resulting breast cancers both in vivo as well as ex vivo using cancer organoids. HP breast cancers showed accelerated tumor formation in vivo and increased invasion and migration in in vitro assays. HP breast cancer cells were resistant to the pan-HER tyrosine kinase inhibitor, neratinib, but were effectively treated with neratinib plus the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan. Proteomic and RNA-seq analysis of HP breast cancers identified increased gene expression of cyclin D1 and p21WAF1/Cip1 and changes in cell-cycle markers. Combining neratinib with CDK4/6 inhibitors was another effective strategy for treating HP breast cancers, with neratinib plus palbociclib showing a statistically significant reduction in development of mouse HP tumors as compared to either drug alone. The efficacy of both the neratinib plus trastuzumab deruxtecan and neratinib plus palbociclib combinations was validated using a human breast cancer patient-derived xenograft with very similar HER2 and PIK3CA mutations to the HP mice. Further, these two drug combinations effectively treated spontaneous lung metastasis in syngeneic mice transplanted with HP breast cancer organoids. This study provides valuable preclinical data to support the ongoing phase 1 clinical trials of these drug combinations in breast cancer. Significance: In HER2-mutated breast cancer, PIK3CA mutation activates p21–CDK4/6–cyclin D1 signaling to drive resistance to HER2-targeted therapies, which can be overcome using CDK4/6 inhibitors.
Availability of LGBTQ Mental Health Services for US Youth, 2014 to 2020
Authors: Kristen R. Choi, Lauren E. Wisk, Bonnie T. Zima
Journal: JAMA Pediatrics (2023)

This survey study reports the variability of lesbian, gay, bisexual, transgender, queer (LGBTQ) youth–specific mental health care in the US from 2014 to 2020.
How can lessons from the COVID-19 pandemic enhance antimicrobial resistance surveillance and stewardship?
Authors: Kamini Walia, Marc Mendelson, Gagandeep Kang, Ramasubramanian Venkatasubramanian, Rina Sinha, Sonam Vijay, Balaji Veeraraghavan, Buddha Basnyat, Camilla Rodrigues, Nitin Bansal, Pallab Ray, Purva Mathur, Ram Gopalakrishnan, Vinod C Ohri
Journal: The Lancet Infectious Diseases (2023)
Deficiency of the Polycomb Protein RYBP and TET Methylcytosine Oxidases Promotes Extensive CpG Island Hypermethylation and Malignant Transformation
Authors: Wei Cui, Zhijun Huang, Seung-Gi Jin, Jennifer Johnson, Kin H. Lau, Galen Hostetter, Gerd P. Pfeifer
Journal: Cancer Research (2023)

Hypermethylation of CpG islands (CGI) is a common feature of cancer cells and predominantly affects Polycomb-associated genomic regions. Elucidating the underlying mechanisms leading to DNA hypermethylation in human cancer could help identify chemoprevention strategies. Here, we evaluated the role of Polycomb complexes and 5-methylcytosine (5mC) oxidases in protecting CGIs from DNA methylation and observed that four genes coding for components of Polycomb repressive complex 1 (PRC1) are downregulated in tumors. Inactivation of RYBP, a key activator of variant PRC1 complexes, in combination with all three 5mC oxidases (TET proteins) in nontumorigenic bronchial epithelial cells led to widespread hypermethylation of Polycomb-marked CGIs affecting almost 4,000 target genes, which closely resembled the DNA hypermethylation landscape observed in human squamous cell lung tumors. The RYBP- and TET-deficient cells showed methylation-associated aberrant regulation of cancer-relevant pathways, including defects in the Hippo tumor suppressor network. Notably, the quadruple knockout cells acquired a transformed phenotype, including anchorage-independent growth and formation of squamous cell carcinomas in mice. This work provides a mechanism promoting hypermethylation of CGIs and shows that such hypermethylation can lead to cell transformation. The breakdown of a two-pronged protection mechanism can be a route towards genome-wide hypermethylation of CGIs in tumors.Dysfunction of the Polycomb component RYBP in combination with loss of 5-methylcytosine oxidases promotes widespread hypermethylation of CpG islands in bronchial cells and induces tumorigenesis, resembling changes seen in human lung tumors.
Digital Technologies in Cardiac Rehabilitation: A Science Advisory From the American Heart Association
Authors: Jessica R. Golbus, Francisco Lopez-Jimenez, Ana Barac, William K. Cornwell, Patrick Dunn, Daniel E. Forman, Seth S. Martin, Erica N. Schorr, Marta Supervia
Journal: Circulation (2023)

Cardiac rehabilitation has strong evidence of benefit across many cardiovascular conditions but is underused. Even for those patients who participate in cardiac rehabilitation, there is the potential to better support them in improving behaviors known to promote optimal cardiovascular health and in sustaining those behaviors over time. Digital technology has the potential to address many of the challenges of traditional center-based cardiac rehabilitation and to augment care delivery. This American Heart Association science advisory was assembled to guide the development and implementation of digital cardiac rehabilitation interventions that can be translated effectively into clinical care, improve health outcomes, and promote health equity. This advisory thus describes the individual digital components that can be delivered in isolation or as part of a larger cardiac rehabilitation telehealth program and highlights challenges and future directions for digital technology generally and when used in cardiac rehabilitation specifically. It is also intended to provide guidance to researchers reporting digital interventions and clinicians implementing these interventions in practice and to advance a framework for equity-centered digital health in cardiac rehabilitation.
Patterns in Child Health Outcomes Before and After the COVID-19 Outbreak in India
Authors: Soohyeon Ko, Rockli Kim, S. V. Subramanian
Journal: JAMA Network Open (2023)

This cross-sectional study examines prepandemic-to-postpandemic changes in mortality, nutrition and feeding practices, anthropometry, vaccination, and other measures in a sample of children from the Indian National Family Health Survey.
Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma
Authors: Jason R. Westin, Olalekan O. Oluwole, Marie José Kersten, David B. Miklos, Miguel-Angel Perales, Armin Ghobadi, Aaron P. Rapoport, Anna Sureda, Caron A. Jacobson, Umar Farooq, Tom van Meerten, Matthew Ulrickson, Mahmoud Elsawy, Lori A. Leslie, Sridhar Chaganti, Michael Dickinson, Kathleen Dorritie, Patrick M. Reagan, Joseph McGuirk, Kevin W. Song, Peter A. Riedell, Monique C. Minnema, Yin Yang, Saran Vardhanabhuti, Simone Filosto, Paul Cheng, Shilpa A. Shahani, Marco Schupp, Christina To, Frederick L. Locke
Journal: New England Journal of Medicine (2023)

In an analysis of the primary outcome of this phase 3 trial, patients with early relapsed or refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, as second-line treatment had significantly longer event-free survival than those who received standard care. Data were needed on longer-term outcomes. Download a PDF of the Research Summary. In this trial, we randomly assigned patients with early relapsed or refractory large B-cell lymphoma in a 1:1 ratio to receive either axi-cel or standard care (two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had a response). The primary outcome was event-free survival, and key secondary outcomes were response and overall survival. Here, we report the results of the prespecified overall survival analysis at 5 years after the first patient underwent randomization. A total of 359 patients underwent randomization to receive axi-cel (180 patients) or standard care (179 patients). At a median follow-up of 47.2 months, death had been reported in 82 patients in the axi-cel group and in 95 patients in the standard-care group. The median overall survival was not reached in the axi-cel group and was 31.1 months in the standard-care group; the estimated 4-year overall survival was 54.6% and 46.0%, respectively (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.54 to 0.98; P=0.03 by stratified two-sided log-rank test). This increased survival with axi-cel was observed in the intention-to-treat population, which included 74% of patients with primary refractory disease and other high-risk features. The median investigator-assessed progression-free survival was 14.7 months in the axi-cel group and 3.7 months in the standard-care group, with estimated 4-year percentages of 41.8% and 24.4%, respectively (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). No new treatment-related deaths had occurred since the primary analysis of event-free survival. At a median follow-up of 47.2 months, axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than standard care. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.) QUICK TAKE VIDEO SUMMARYSurvival with Axi-cel in Large B-Cell Lymphoma 02:09
Patterns in the Economic Burden of Acute Kidney Injury in Hospitalized Children, 2019-2021
Authors: Rupesh Raina, Anvitha Soundararajan, Natalie Menassa, Aadi Pandya, Carla Nemer, Abhishek Tibrewal, Sidharth Kumar Sethi
Journal: JAMA Network Open (2023)

This economic evaluation uses data from the Pediatric Health Information System to assess patterns in the economic burden of acute kidney injury and variables correlated with mortality and length of stay among hospitalized US children with acute kidney injury between 2019 and 2021.
Drug content on anticancer efficacy of self-assembling ketal-linked dextran-paclitaxel conjugates
Authors: Tiantian Guo, Haiping Zhong, Xingwei Li, Jingqing Mu, Tao Liu, Na Yu, Yang Zhao, Xing-Jie Liang, Shutao Guo
Journal: Journal of Controlled Release (2023)
National Trends in Physical Activity Among Adults in South Korea Before and During the COVID-19 Pandemic, 2009-2021
Authors: Sangil Park, Hyeon Jin Kim, Sunyoung Kim, Sang Youl Rhee, Ho Geol Woo, Hyunjung Lim, Wonyoung Cho, Dong Keon Yon
Journal: JAMA Network Open (2023)

There is a lack of comprehensive data on the association of the COVID-19 pandemic with the prevalence of physical activity in large-scale data sets.
Germline Genetic Testing After Cancer Diagnosis
Authors: Allison W. Kurian, Paul Abrahamse, Allison Furgal, Kevin C. Ward, Ann S. Hamilton, Rachel Hodan, Rachel Tocco, Lihua Liu, Jonathan S. Berek, Lily Hoang, Amal Yussuf, Lisa Susswein, Edward D. Esplin, Thomas P. Slavin, Scarlett L. Gomez, Timothy P. Hofer, Steven J. Katz
Journal: JAMA (2023)

Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention.
In older adults, an Ad26.RSV.preF-RSV preF protein vaccine reduced RSV-related lower respiratory tract disease
Authors: Melina Awar, Eleftherios Mylonakis
Journal: Annals of Internal Medicine (2023)

Source Citation Falsey AR, Williams K, Gymnopoulou E, et al; CYPRESS Investigators. Efficacy and safety of an Ad26.RSV.preF-RSV preF protein vaccine in older adults. N Engl J Med. 2023;388:609-620. 36791161